Ionic ReactionsNucleophilic Substitution and Elimination

Reactions of Alkyl Halides

Organic HalidesAlkyl Halides: alkane molecule in which a

halogen has replaced a hydrogen

R

H

H

X

R

R

H

X

R

R

R

X

1o 2o 3o

X = Cl, Br, IC X

Physical Properties Of Organic HalidesLow solubilities in waterMiscible with each other and other relatively

nonpolar solventE.g CH2Cl2 CHCl3 CCl4

Reaction Intermediates3 major types

Carbocation (C+)Carbanion (C-)Free radical (C· )

Reaction SitesNucleophiles: (nucleus-loving) any species

containing electron pairsElectrons are (-), so Nu: are attracted to (+)

siteCharge Nu: are better than neutral oneE.g H O CH3CH2 OH H OH H3C NH2 CH3CH2 SH

Reaction SitesElectrophiles (electron-loving): any species

or site in molecule that’s deficient in electron density because it’s near a electronegative atom or lacking of e- altogether

O

H3CH2C Cl C

H3C CH3

H

Polar bonds

Multiple bondsThe electrons are available to be donated to

another species

C C C C

alkene alkyne

Nucleophilic Substitution ReactionsGeneral Reaction

Nu: + R X R Nu + X

Nucleophile Alkyl halide Product Halide ions

donates an electronpair to the substrate

The bond betweenthe carbon and the leaving group breaks, givingboth electrons from the bond to the leaving group

The nucleophileuses its electronpair to form a new covalent bondwith the substrate carbon

The leaving groupgains the pair ofelectrons that originally bondedto it in the substrate

Nu: + R Nu R X Nu R X+X

forming breaking

Nu: + R L R Nu + L

charged nucleophile L= leaving group

Nu: + R L R Nu + L

neutral nucleophile L - leaving group

Leaving GroupsRelatively stable, weakly basic molecule or

anionHalogen atom of an alkyl halide is a good

leaving group because once departed it is a weak base and table anion

A mechanism for SN2ReactionThe nucleophile approaches the carbon

bearing the leaving group from the back sideDirectly opposite the leaving groupAs the reaction progresses, the bond between

nucleophile and the carbon strengthens, and the bond between the carbon atom and the leaving group weakens

Carbon atom has its configuration turned inside out inversion

Transition StateArrangement of the atoms in which

nucleophile and the leaving group are both partially bonded to the carbon atom undegoing substitutionBond breaking and forming and occurred

simultaneouly Concerted reaction

Kinetics of a Nucleophilic substitution: an SN2 reaction1 step reactionSecond orderRate of reaction depends an alkyl halides and

Nu:Rate Rxn = k [alkyl halide] x [Nu:]

Stereochemistry of SN2 ReactionsNucleophiles approaches from the back side,

that is directly opposite the leaving group.Consider the cis-1-chloro-3-

methylclyclopentaneWhen undergoes SN2, the product become

trans

examplesGive the structure of the product that would

be formed when trans-1-bromo-3-methylcyclobutane undergoes an SN2 reaction with NaI

C L L

C

Step 1: halide ionleaves with its pair of electrons,leaving a carbocation intermediate

carbocation intermediateachiral C+

HNu:

A BH3

CNu

A

C Nu

B

enantiomersresulted from racemization

Step 2: Nucleophile can attack planar carbocationfrom either side. It uses its nonbonding electron pairfor bonding and neutralizes the carbocation

- H

The Relative stabilities of CarbocationsThe order of stability of carbocations can be

explained on the basic of hyperconjugation.Involves electrons delocalization from a filled

bonding orbital to an adjacent unfilled orbitalAny time a charge can be disperred or

delocalized, a system will be stabilized

C

R

R

R C

R

H

R C

H

H

H> >

3o 2o 1o

There is more overlaping of the vacant p orbital in 3o than 2o and 1o

HC

H

HH

CH

H

Vacant p orbital

orbitals overlap here

Kinetics of a Nucleophilic substitution: an SN1 reaction2 step reaction1st order rate determinationRate of reaction depends the slowest step

Heterocleavage of halideRate Rxn = k [alkyl halide]

Multistep Reactions and The Rate-Determining Step

Multistep Reactions and The Rate-Determining StepThe step is intrinsically slower than all other

is called the rate-limiting step or rate determining stepReactant intermediate 1 intermediate 2 productk1

k2 k3

(slow) (fast) (fast)

Step 1 Step 2 Step 3

k1 << k2 < k3

Transition StateStabilization of leaving group

I- > Br- > Cl- > F-

Weaker conjugated base stronger leaving group

C X C X

T.S

C + X

Mechanism for SN1 ReactionShow a complete mechanism with

stereochemisty for the following reactionCH3

Cl + 2H2O

CH3

H3CH3C

H3CH3C

OH

CH3

HOCH3

CH3

+

Mechanism for SN1 ReactionShow a complete mechanism with

stereochemisty for the following reaction

Br + 2 CH3OH

Factors Affecting the Rates of SN1 and SN2 ReactionsThe structure of the substrate,The concentration and reactivity of the

nucleophileThe effect of the solventThe nature of the leaving group

The Effect of the Structure of the substrateSN2 reaction shows the following general

order of reactivity Methyl > primary > secondary >> (tertiary –

unreactive) steric hindrance

SN1 reaction Tertiary > secondary > methyl

Hyperconjugation between p orbitals

Hammond-Leffler PostulateThe structure of a transition state resembles

the stable species that is nearest it in free energy

The effect of the Concentration and Strength of the NucleophileA negatively-charged nucleophile is always a more

reactive nucleophile than its conjugated acidHO- is a better Nu: then H2O and RO- is better than

ROH

In a group of nucleophiles in which the nucleophilic atom is the same, nucleophilicities parallel to basicitiesRO- > HO- >> RCO2

- >> ROH > H2O equilibrium favors the side with weaker acid

Solvent Effects on SN2 Reactions: Polar Protic and Aprotic solventThe effect of hydrogen bonding with the

nucleophile is to encumber the Nu: and hinder its reactivity in a substitution reaction

X HH

H

H

OH

O

H

OH

O

H

Molecules of the protic solvent, water, solvatea halide ion by forming hydrogen bonds to it

Solvent Effects on SN2 Reactions: Polar Protic and Aprotic solventHydrogen bonds to a small nucleophile atom

are more stronger than those to larger nucleophilic atomsHalide Nucleophilic in Protic SolventI- > Br- > Cl- > F-

Larger atoms have greater polarizability larger nucleophile atom can donate a greater degree of electron density to substrate

SH- > CN- > I- > -OH > N3- > Br- > CH3CO2

- > Cl- > F- > H2O

Solvent Effects on SN2 Reactions: Polar Protic and Aprotic solventAprotic solvents are those solvents whose

molecules do not have a hydrogen that is attached to an atom of an electronegative element

They do the same way as protic solvents solvate cations; by orienting their negative ends around cation and by donating unshared electron pairs to vacant orbitals of the cation

Solvent Effects on SN2 Reactions: Polar Protic and Aprotic solventThey cannot form H-bond because their

positive centers are well shielded by the steric effects from any interaction with anions

Rate of SN2 reaction generally increased when they are carried out in a polar protic solvent

Solvent Effects on SN1 Reactions: The Ionizing Ability of the solventThe use of polar protic solvent will greatly

increase the rate of ionization of an alkyl halide in SN1 reactionAble to solvate cations and anions more

affectivelyStabilize transition state leading to the

intermediate carbocation and halide ion more than it does the reactant

Lower activation energyH3C

CH3

Cl

CH3

H3C

CH3

Cl

CH3

H2O H3C

C

H3C

CH3

Transition stateseparated charges are developing

Summary of SN1 and SN2 ReactionsFactor SN1 SN2Substrate 3o (requires formation of a

relatively stable carbocation)

Methyl > 1o > 2o (requires unhindered substrate)

Nu: Weak Lewis base, neutral moleculeNu: may be the solvent

Strong Lewis Base, rate increased by high concentration of Nu:

Solvent Polar Protic (e.g alcohol, water…)

Polar protic (e.g DMF, DMSO

Leaving Group: I > Br > Cl > F for both SN1 and SN2 ( the weaker the base after the group departs the better the leaving group)

Elmination Reactions of Alkyl HalidesGeneral ReactionIf carbon next to alkyl halide has a halogen,

Elimination is possibleRequire a strong base

C C

Y Z

elimination

- YZ

DehydrohalogenationGeneral ReactionElements of hydrogen halide are eliminated

from a haloalkane

C C

H X

+ B + H B + X-

1,2 EliminationAlpha (α) carbon atom: carbon that bears the

substituentBeta (β) hydrogen atom: hydrogen that

attached to the carbon adjacent to α carbon

C C

H X

2 R OH + 2 Na 2 R O + Na + H2

Conjugated base of an alcohol with alkali metal

HOH + 2 Na 2 HO Na + H2

Oxidation-Reduction reaction

R O H + Na H R O Na H H

Sodium alkoxide

2 CH3CH2OH + 2 Na 2 CH3CH2O Na + H2

Ethanolexcess

sodium ethoxide

CH3

OHH3C

CH3

+ 2 K

CH3

OH3C

CH3

K + H2

tet-Butyl alcohol(excess)

Potassium tert-butoxide

Nu:

H

X X

H

Nu:T.Sforming

broken

breaking

+ HNu + X

Nu: removes H atom fromcarbon. At the same timethe electron pairs begin to forma double bond and halogen ionbegins to depart with a pair ofelectron

Partial bonds in the transition statedouble bond is fully formed andalkene has a trigonal planar

ExampleShow a complete mechanism for E2 reaction

CH3O + CH3CHBrCH3CH2 CHCH3 + CH3OH + Br-

Mechanism for E1 ReactionUnimolcular reaction

H

X

H

Nu:

Aided by the polar solventhalide departs with the electrons

carbocation is produced from theslow step reaction.Nu: removes H atom fromcarbon. At the same time anelectron pair move in to formdouble bond

+ HNu + X

ExampleShow a complete mechanism for E1 reaction

CH3CH2Br + H2O H2C CH2 + H3O- + Br-

Substitution Versus ElminationAs a rule:

If your subsitution mechanism is SN1, E1 is the elimination mechanism

If your substitution mechanism is SN2, E2 is the elmination mechanism

2o alkyl halides: if 2o ; weak Nu: E1 if 2o; strong Nu: E2

H X

NuH

Elimination

Substitution

Nu: / Nu:

ExamplesProve the possible mechanisms (SN1, SN2, E1

and/or E2) and possible products for the reaction below

Cl

+ OH